Systems and methods to optimize anti-tachycardial pacing (atp)

ABSTRACT

Apparatus, systems and methods are provided for prevention and/or remediation of cardiac arrhythmias, e.g. optimizing anti-tachycardia pacing (ATP) algorithms. More particularly, implantable devices are provided that measure and treat cardiac arrhythmias. By monitoring the ATP attempt from additional electrodes, far-field morphology analyses, and/or measuring the return interval from a failed ATP attempt; the devices may estimate when entrainment has occurred, the amount of delay within the reentrant tachycardia, and/or tachycardia termination/acceleration. These variables and occurrences can be used to optimize the first and/or subsequent ATP attempts. Furthermore, other exemplary embodiments describe methods to integrate electrical restitution properties into the design of ATP pacing algorithms to facilitate tachycardia termination.

RELATED APPLICATION DATA

This application is a continuation of co-pending application Ser. No.14/811,719, filed Jul. 28, 2015, issuing as U.S. Pat. No. 9,795,789,which claims benefit of provisional application Ser. No. 62/030,520,filed Jul. 29, 2014, the entire disclosure of which is expresslyincorporated by reference herein.

FIELD OF THE INVENTION

This invention is in the field of devices and methods to diagnose andtreat cardiac arrhythmias.

BACKGROUND

Abnormally fast heart rates are called tachycardias. When thetachycardia occurs in the top chambers of the heart (the atria), this istermed atrial tachycardia. When it occurs in the bottom chambers (theventricles), this is termed ventricular tachycardia. These rhythms canbe highly symptomatic in the case of atrial tachycardia or can belife-threatening in the case of ventricular tachycardia.

These rhythms are often due to diseased or dead myocardial tissue, whichmay form a scar. Under normal conditions, all myocardial cells conductelectrical activity. When a myocardial cell depolarizes, the ionicmembrane potential changes; which as a result, can cause its neighbormyocardial cell to depolarize, and so on. Therefore, depolarizing cellsresult in a self-propagating mechanism, whereby depolarizing wavefrontstravel through myocardial tissue. In certain settings, a propagatingwavefront may travel around non-conducting tissue. If each cell alongthis reentrant pathway has enough time to repolarize the cell's membranepotential, the resulting wavefront can then get caught in a perpetualloop where the electrical signal in the myocardial tissue circles arounda fixed point or central scar. The action potentials will continuallypropagate around the non-conducting tissue (such as a prior myocardialinfarction) at a rate considerably faster than the heart's intrinsicrate. The reentrant circuit can be thought of as a conduction wavefrontpropagating along a tissue mass of approximately circular geometry.

Initially, these dangerous rhythms were treated with an external shock(defibrillation) that resets the myocardial tissue to regain normalsinus rhythm. As implanted devices became more complex, pacingmodalities were created to attempt to pace-terminate the tachycardia.This is termed anti-tachycardia pacing (ATP). When ATP strategies fail,the device may then proceed with painful how powered shocks; whichusually are very painful to the patient. ATP, on the other hand, isusually painless.

The rate at which myocardial tissue can allow a propagating wavefront toconduct through it has a limit. Once depolarized, the tissue mustrepolarize in order to conduct another propagating wavefront. If awavefront approaches myocardial tissue which has not repolarized thetissue cannot conduct the wavefront and the electrical signal willterminate. Tissue that has not yet repolarized and cannot conduct anelectrical signal is termed refractory.

To terminate an arrhythmic circuit, a pacing stimulus is provided at atime and location such that the resulting wave propagation fails toconduct down the pathway of the reentrant circuit. When pacing fasterthan the reentry tachycardia, the paced stimulation wavefront proceedstoward the arrhythmic circuit. This wavefront can approach both sides ofthe reentrant circuit (see FIG. 4 for clarity); such that the wavefrontwill collide with the wavefront leaving the reentrant circuit (termedthe ‘exit’ site). With more pacing, the paced wavefront will reach thenative tachycardia prior to the reentrant wavefront; resulting in anearlier depolarization of the reentrant circuit. With substantiallycontinuous pacing, we can reach “entrainment,” whereby the wavefronttraveling towards the exit site, will collide with the wavefront fromthe prior wavefront within the arrhythmic circuit (in the retrogradedirection). The paced wavefront will also proceed towards the entrancesite of the reentrant tachycardia and proceed down the path of thearrhythmic circuit in the orthograde direction. If the pacing rate isaccelerated, this orthodromic wavefront may reach a part of thearrhythmia circuit before it has repolarized and is thereforerefractory. If this occurs, the wavefront may terminate and thearrhythmia will end. Accordingly, the probability of anti-tachycardiapacing (ATP) succeeding in terminating a tachycardia is related to theability of the pacing stimulation wavefront to arrive at the location ofthe reentrant circuit in such a manner that the propagating signal inthe reentrant circuit is modified, is unable to perpetuate thepropagating signal, and the tachycardia is terminated.

Numerous different pacing modalities and algorithms have been createdfor the termination of tachycardia. These algorithms have been createdfor both atrial and ventricular tachycardias. These algorithms areprogrammed into implanted devices such as a pacemaker or implantablecardioverter-defibrillators (ICDs). These devices may deliver a highpowered electrical shock which attempts to reset all cells involved inthe reentrant tachycardia in order to terminate the tachycardia. Theseshocks are often painful and can cause harm to myocardial cells.Alternatively, the devices may deliver anti-tachycardia pacing (ATP),whereby paced wavefronts reach critical aspects of the reentrant circuitin such a manner that the tachycardia terminates. ATP is usuallypainless and therefore has advantages over high-powered cardioversions.

ATP is not always successful at terminating the tachycardia. In thiscircumstance, the ATP is repeated at the same or different pacingalgorithm in attempts to terminate the arrhythmic into a normal sinusrhythm. If ATP is unsuccessful, the patient may require high voltagecardioversion. ATP is unsuccessful in approximately 10-40% of ATPattempts. In addition, ATP sometimes accelerates the rhythm to a fasterrate or may degenerate the rhythm into ventricular fibrillation, whichis a chaotic rhythm that is not capable of sustaining life. Furthermore,the longer the patient is in ventricular tachycardia, the more likelythe patient is to pass out (syncope) which is dangerous.

Thus, improved methods for increasing the success rate of ATP and fordecreasing the time in tachyarrhythmia, which will reduce the need forpainful ICD shocks, are needed.

ATP often functions by entraining the tachycardia. Entraining is aprocess whereby paced beats (by a pacemaker lead, for example)accelerates the tachycardia. One or more stimulations are provided at arate slightly faster than the tachycardia, such that the pacedwavefronts enter and accelerate the tachycardia. The first pacedstimulation that advances the reentrant tachycardia resets thetachycardia. The next pacing stimulation typically advances thetachycardia to the paced cycle length. Since myocardial tissueproperties often change in response to shorter cycle lengths, severalresetting stimulations may be needed to completely advance thetachycardia to the pacing cycle length. Each paced beat then ‘resets’the tachycardia to the faster rate, termed entrainment. Ideally, thefaster rate is too fast for the arrhythmic circuit, such that the tissuehas not had enough time to repolarize. In this case, the wavefrontterminates, and the patient returns to sinus rhythm.

Entrainment involves identifying a specific response of a reentrantarrhythmia to external pacing, including: (1) beat to beat interactionbetween the paced and tachycardia wavefront; (2) activation of all thetissue in the chamber where the circuit is located; and (3) persistenceof the tachycardia after pacing, if the tachyarrhythmia does notself-terminate. If the self-sustaining tachyarrhythmia of the heart isthought of as an electrical circuit running in a circle, one can“entrain” that circuit by pacing slightly faster than the circuit wasrunning on its own. This is known as resetting the circuit, as thetissue in the circuit will now be excited at the new, faster, pacedrate, as compared to the pace at which the circuit ran on its own beforeentrainment. If the circuit can propagate at the faster rate, when thisre-setting is stopped, the pacing catheter electrode in the heart canthen measure the time required for the last paced beat to create awavefront, enter the arrhythmic circuit, propagate around a portion ofthe arrhythmic circuit, and then exit to the same electrode or catheter.This time is termed the post-pacing interval (PPI). The post-pacinginterval has long been used as an indication of the proximity of thepacing site to the reentry circuit. (Stevenson, Khan et al. 1993) (Waldo1997).

The efficacy of the delivery of anti-tachycardia pacing (ATP) throughthe right ventricular implantable cardioverter defibrillator (ICD) leadto terminate life-threatening fast ventricular tachycardia (FVT) wasfirst published in 2001 by Wathen et al. In this study, the authorsrevealed that ATP could prevent ICD shock delivery in 3 of 4 episodes.Over the following years, ATP has become a valuable option to treat mostVT episodes. Large-scale studies, including PainFree Rx II, EMPIRIC,PREPARE, or ATPonFastVT, have demonstrated the efficacy and safety ofthis approach. Moreover, delivering ATP instead of defibrillation hasdramatically reduced the number of painful ICD shocks.

Typically, the ATP algorithm depends on the type (atrial versusventricular) and rate of the tachycardia. For example, most devicemakers make a distinction between ventricular tachycardia (VT), fastventricular tachycardia (FVT), and ventricular fibrillation (VF) basedon the rate of the tachycardia. The tachycardia rate can be described interms of beats per minute (BPM) or can be thought of as the time betweenheart beats (termed the RR interval). This time is also termed thetachycardia cycle length (TCL), and is often given in milliseconds.60,000 divided by the heart rate provides the cycle length inmilliseconds (ms). For example, a tachycardia of 200 BPM has atachycardia cycle length of 300 ms.

ATP can be a pacing train of a certain cycle length (burst pacing) orcan shorten the cycle length with each additional paced beat (oftentermed ramp pacing). Ramp therapy consists of a decremental drive of aprogrammable number of pulses, starting at a rate proportional to thecurrent tachycardial cycle length (TCL).

The current algorithms of ATP are well known and easily accessible. Oneexample (described below) is by implantable device maker Medtronic,although all device makers have created similar pacing algorithms.

In Medtronic's PainFREE Rx II Trial, the first therapy in the FVT zone(188-250 BPM) was 2 ATP sequences (8-pulse burst pacing train at 88% ofthe FVT cycle length). If the first ATP sequence was unsuccessful, thesecond sequence was delivered at 88% of the FVT cycle length minus 10ms. ATP therapies were delivered at maximum voltage and pulse duration.Programming of subsequent FVT therapies was left to the investigators'discretion and usually involved ICD shocks.

A recent study by Martins et al published in Eurospace (2012) performeda study involving the major ICD device makers: Biotronik, BostonScientific, Medtronic, St Jude Medical and Sorin Group companies. Inthis study, the ventricular ATP algorithm was as follows: Implantablecardioverter/defibrillators were programmed to deliver 10 ATP attemptsfor FVT cycle lengths (CLs) of 250-300 ms (200-240 BPM) before shockdelivery (5 bursts, then 5 ramps; 8-10 extrastimuli at 81-88% FVT CL;minimal pacing CL 180 ms). A total of 1839 FVTs, 1713 of which wereATP-terminated (unadjusted efficacy 1/4 93.1%, adjusted 1/4 81.7%).Furthermore, over 20% of the patient experienced ATP that required morethan two episodes of ATP.

Thus, there is room to improve the current ATP algorithms to reduce thetime spent in tachycardia and prevent ICD shock.

The most advanced pacemakers feature atrial preventive pacing and atrialanti-tachycardia pacing (DDDRP), which may reduce atrial fibrillationoccurrence and duration. The device automatically delivers ATP therapieswhen an episode is classified as atrial tachycardia and lasts longerthan a programmable ‘time to first therapy’ (often 1 min). Often, rampis programmed in order to deliver three series of ten sequences each, sothat each patient could receive up to thirty termination attempts. Eachseries begins with a train of ten pulses. The first pulse of each of thethree series is delivered at 91, 84, and 81% of the underlying atrialtachycardia cycle length (ATCL), respectively. In each series,subsequent pulses were delivered with a decrement in pacing couplinginterval of 10 ms each. If a previous train fails to terminate AT, anadditional stimulus is added to the next train.

Burst+ therapy uses a drive of a programmable number of atrial pulses,the rate of which is proportional to the current ATCL, followed by up totwo extrastimuli. Burst+ is programmed in order to deliver three seriesof ten sequences each; each sequence is made up of fifteen pulsesfollowed by two extrastimuli. As in the Ramp programming, each patientcan receive up to thirty termination attempts. The first scan of eachseries is released at 84% of the underlying ATCL. The firstextrastimulus is delivered at 81% of the underlying ATCL; the secondextrastimulus was delivered with an interval reduced by 20 ms. In theevent of failure, the ATP train coupling interval was decreased by 10 msfor each subsequent scan.

For both therapies, the minimal pacing interval (MPI) was 150 ms, sothat pulses programmed at a shorter pacing interval than the MPI weredelivered at the MPI value. Atrial ATP was recently found tosignificantly reduce the progression of atrial tachycardia to permanentatrial fibrillation (61% relative risk reduction) over a 2 yearfollow-up.

Previous methods use similar strategies for all tachycardias. Thesestrategies use a burst or a ramp strategy with variable number of beats.If this ATP attempt fails, another burst or ramp is delivered at shorterintervals (faster rates). We have devised unique pacing algorithms basedon novel concepts to improve the ability of a device to terminate atachycardia.

SUMMARY

The present invention is directed to apparatus, systems and methods forprevention and/or remediation of cardiac arrhythmias, e.g. optimizinganti-tachycardia pacing (ATP) algorithms. More particularly, the presentinvention is directed to implantable devices that measure and treatcardiac arrhythmias. By monitoring the ATP attempt from additionalelectrodes, far-field morphology analyses, and/or measuring the returninterval from a failed ATP attempt; the present application describesexamples where the device estimates the timing of entrainment, theamount of delay within the reentrant tachycardia, and/or tachycardiatermination/acceleration. These variables and occurrences can be used tooptimize the first and/or subsequent ATP attempts. Furthermore, otherexemplary embodiments describe methods to integrate electricalrestitution properties into the design of ATP pacing algorithms tofacilitate tachycardia termination.

In one exemplary embodiment, the device may identify reentranttachycardias based on timing intervals, far-field morphology, and/or thetime differences between multiple electrodes. The device may alsomonitor for arrhythmia entrainment and/or termination during deliver ofATP to optimize the current and future ATP algorithms. By measuringdynamic responses occurring from overdrive pacing from far-fieldmorphology and/or timing intervals of cardiac signals from additionalelectrode(s), other embodiments herein may estimate and record certainaspects of the ATP attempt, such as the total premature pacing timerequired to entrain the tachycardia (“the Time to Entrainment”),conduction delay occurring within the tachycardia circuit (the “TimeDelay”), changes in the tachycardia (such as tachycardia acceleration),tachycardia termination, and the prior successfulness and failures ofcertain ATP strategies. As is described in the following text andfigures, the device can use these measurements and occurrences toimprove the probability of tachycardia termination by leveragingelectrical restitution properties of myocardial tissue. Examples aredescribed herein of organizing the initial pacing intervals to minimizepartial tachycardia acceleration as well as the strategy of delivering“priming” pacing pulses, or pulses delivered at longer intervals thantypically seen in anti-tachycardia pacing attempts; in efforts to slowrepolarization rates in critical aspects of the arrhythmic circuit.These methods will therefore improve the successfulness of ATP attempts,decrease the time the patient spends in dangerous tachyarrhythmias, andreduce the need for ICD shocks. Therefore, the following concepts areadvantageous to programming and designing device ATP capabilities andalgorithms.

Other aspects and features of the present invention will become apparentfrom consideration of the following description taken in conjunctionwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

In general, examples disclosed herein are directed to treatingtachyarrhythmias, such as ventricular tachycardia, by employing at leastone electrode to deliver electrical stimulation to a patient's heart ina manner designed to terminate a tachyarrhythmia episode.

FIG. 1 reveals a schematic diagram of a pacemaker/implantablecardio-defibrillator (ICD) with specialized leads going into the heartin which the present invention may be usefully practiced.

FIG. 2 is a functional block diagram of the circuitry located in theimplantable pacemaker/cardioverter/defibrillator of FIG. 1.

FIG. 3 is a graphical representation of overdrive pacing from oneelectrode while sensing electrical depolarizations from a secondelectrode. The Fig helps demonstrate how timing measurements can beperformed to estimate the Time to Entrainment.

FIGS. 4A and 4B reveal an example of intracardiac and far-fieldmorphologies which illustrate how far-field morphology analyses can beutilized to estimate the Time to Entrainment.

FIG. 5 is a simplified diagram of a reentrant tachycardia circuit withina heart and several pacing electrodes for sensing and/or deliveringelectrical stimulations according to an exemplary embodiment.

FIG. 6 reveals the relationship between the coupling intervals during apacing drivetrain and the effective refractory period, also known as theelectrical restitution curve.

FIG. 7 is a graphical representation explaining how the paced cyclelength and number of stimulations affects the amount of tachycardiaacceleration on the first entrained stimulation.

FIG. 8 reveals an example of utilizing intracardiac measurements andfar-field morphology analyses to determine the Time to Entrainment andTIMF Delay within the circuit taken from an ATP attempt from anepicardial electrode.

FIG. 9 is a flow diagram illustrating an exemplary process for applyingan ATP therapy according to an exemplary embodiment utilizing prior ATPattempts, return cycle intervals (aka post-pacing intervals), far-fieldmorphology analyses, and/or at least one additional electrode.

FIG. 10 is a flow diagram further illustrating an exemplary process forapplying an ATP therapy according to an embodiment in the presentinvention utilizing prior ATP attempts, return cycle intervals (akapost-pacing intervals), and/or far-field morphology analyses.

FIG. 11 is a graphical representation of anti-tachycardia pacing (ATP)according to an exemplary embodiment.

DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

Overdrive pacing is typically performed at a rate faster than the nativetachycardia; therefore the paced cycle length is usually shorter thanthe tachycardia cycle length (PCL<TCL). Each paced stimulation ‘gains’on the native tachycardia by the amount of pacing prematurity, or thedifference between the tachycardia cycle length and overdrive pacingcycle length (TCL−PCL). Overdrive pacing continues to ‘gain’ on thenative tachycardia until the paced wave front reaches and thenaccelerates the native tachycardia. Once overdrive pacing reaches thearrhythmic circuit, additional pacing stimulations continuously resetsthe native tachycardia to the PCL (entrainment). Therefore, the totalamount of time overdrive pacing “gains” on the native tachycardia beforepacing begins to accelerate/reset the native tachycardia can becalculated in equation 1 based on the number of pacing simulationsrequired to accelerate the tachycardia (n), the difference between thetachycardia cycle length and the paced cycle length (TCL−PCL) [which canbe variable], minus the amount of tachycardia acceleration.

$\begin{matrix}{{{Time}\mspace{14mu} {Gained}} = {{\sum\limits_{0}^{n}\left( {{TCL} - {PCL}} \right)} - {{tachycardia}\mspace{14mu} {advancement}}}} & (1)\end{matrix}$

A distant electrode may be able to monitor the TCL during overdrivepacing and estimate the timing of tachycardia entrainment and conductiondelay within the reentrant tachycardia. The total amount of timeoverdrive pacing needs to gain on the native tachycardia in order toentrain the tachycardia can be approximated by the post-pacing intervalminus the tachycardia cycle length (PPI−TCL). The postpacing interval(PPI) or the return interval (RI) is the return interval that occursafter an entrainment maneuver or a failed ATP attempt. This time is thetime required for the paced signal to travel from the pacing location,around the reentrant circuit, and then back to the pacing electrode. Thefaster the overdrive pacing cycle length, or the faster theanti-tachycardia pacing cycle length, the return cycle will prolong dueto conduction velocity slowing; primarily in the reentrant circuit.

The total amount of time overdrive pacing must overcome in order toattain entrainment can be mathematically determined. The return cycle ofthe compensatory pause is equal to the TCL plus the amount of pacingprematurity (TCL−PCL). With additional pacing stimulations, the returncycle of the compensatory pause continues to prolong with each pacedstimulation (equation 2). Once pacing reaches the arrhythmic circuit,the paced wavefront accelerates the native tachycardia, and the returncycle is shorter than would be predicted from a compensatory pause.Assuming minimal changes in conduction velocity, the return cycle of thefirst entrained beat, as well as all additional pacing stimulations,will be fixed at the PPI. In reality, there can be significantprolongations in the post-pacing interval secondary to changes inconduction velocity at a shorter cycle length. Generally, theuncorrected PPI can be determined by adding the tachycardia cycle lengthto the total amount of pacing prematurity, minus the amount oftachycardia advancement (equation 3).

Compensatory Pause

Return interval=TCL+stim number(n)*(TCL−PCL)  (2)

At Entrainment

PPI=TCL+n*(TCL−PCL)−tachycardia advacement   (3)

As can be seen, by re-arranging equation 3, the total amount of timegained by overdrive pacing must be equal to the PPI−TCL, which is alsoequal to the entrainment time, as can be seen in Equation 4.

$\begin{matrix}{{{PPI} - {TCL}} = {{{n*\left( {{TCL} - {PCL}} \right)} - {{tachycardia}\mspace{14mu} {advancement}}} = {{Entrainment}\mspace{14mu} {Time}}}} & (4)\end{matrix}$

Finally, after adjusting for the slowing that occurs associated with thefaster overdrive pacing (discussed in detail later), we can determinethe corrected PPI, or PPIc; as well as the amount of conduction delay(time delay). By knowing this measurement, we can determine the numberof pacing stimulations required to reach and accelerate the tachycardiaat any cycle length, as shown in equation 5.

$\begin{matrix}{\frac{{PPI}_{C} - {TCL}}{{TCL} - {PCL}} = {{number}\mspace{14mu} {of}\mspace{14mu} {pacing}{\mspace{11mu} \mspace{11mu}}{stimulations}\mspace{14mu} (n)\mspace{14mu} {required}\mspace{14mu} {to}{\mspace{11mu} \;}{advance}\mspace{14mu} a{\mspace{11mu} \;}{tachycardia}{\mspace{11mu} \;}{at}\mspace{14mu} {any}\mspace{14mu} {given}\mspace{14mu} {PCL}}} & (5)\end{matrix}$

The following pacing stimulation will entrain the tachycardia to thePCL. When the tachycardia has been entrained, all electrodes within thepacing chamber (whether the atria or ventricles) will accelerate to thepaced cycle length. Therefore, by having an electrode in the myocardialtissue receiving the depolarized wavefront exiting the reentranttachycardia, the timing of entrainment can be estimated. Furthermore,the amount of delay within the reentrant circuit can be estimated withthis electrode. In some circumstances, the time to entrainment can bedifficult to estimate, even with optimal locations of the distalelectrodes. This error can occur because the first stimulationaccelerating the native tachycardia can introduce significant conductiondelay, which may not be fully appreciated. Therefore, in somecircumstances, overdrive pacing from more than one location can beperformed. In this scenario, the entrainment time for electrode B can bedetermined by equation 6, where the time differences between theelectrodes during entrainment at more than one location are utilized toestimate the entrainment time for electrode B. This equation assumes theoverdrive pacing cycle length is similar for all entrainments.

Entrain Time B=Stim_(A→B)+Stim_(B→A)−PPI_(A→A)   (6)

The PPI−TCL is equal to the sum of the pacing prematurity untilentrainment is obtained. Furthermore, the PPI−TCL is also equal to thetime difference between the pacing electrode and a distal electrodebetween an entrained tachycardia and the reentrant tachycardia. Asimilar method, which relies upon the post entrained stimulation (asopposed to the baseline interval) has been described by Stevenson as theN+1 rule (Friedman, 2001). Furthermore, because conduction tissue mayslow with shorter cycle lengths or persistent pacing, the amount ofconduction delay can be estimated by the time difference between thefirst entrained stimulation and a stable conduction time with persistentpacing. The prolongation in this time from persistent pacing or shortercycle lengths can be used to estimate the conduction delay within thereentrant circuit.

Additionally, far-field waveform morphology analyses can help determinewhen a tachycardia has been entrained and the amount of conduction delaywithin the reentrant circuit. This is because during entrainment, thefar-field morphology is the fusion between the paced morphology and thereentrant morphology. The differences between the far-field pacedmorphology, baseline reentrant morphology, and the fusion morphology canbe used to estimate the timing of entrainment and the amount of delaywithin the reentrant circuit. With persistent pacing at a cycle lengthshorter than the tachycardia cycle length, there is progressive fusionbetween the paced waveform and the tachycardia waveform. When overdrivepacing results in a stable far-field morphology that is distinct withthe far-field morphology that occurs with pacing from the pacinglocation, this finding identifies the tachycardia as entrained. Similarto a distal electrode analysis, the prematurity from each overdrivepacing pulse is aggregate until they sum to the entrainment time; atwhich point the pacing pulses accelerate the native tachycardia. Theprematurity can be summed until the steady fusion morphology isobtained. Furthermore, by comparing the morphology between the far-fieldpaced morphology at baseline, the baseline tachycardia morphology, andthe fusion morphology of an entrained (and stable) tachycardia from thepacing electrode, the entrainment time can be estimated. Furthermore, ifthe morphology significantly changes to match the baseline pacedmorphology; this provides evidence of tachycardia termination.Furthermore, by comparing the Entrainment time and fusion morphologyover a series of pacing stimulation, the Time delay occurring within thetachycardia circuit can be estimated. These variables can be combined todetermine the optimal initial pacing algorithm to minimize partialacceleration; in addition, these variables can be used to optimize the“priming” pulse, to facilitate tachycardia termination.

The difference in time between the electrodes during the reentranttachycardia can be used to estimate the time to entrainment. This isbecause the entrainment pathway may involve certain aspects of thetachycardia reentrant tachycardia. Since the conduction times betweenthe electrodes can be measured prior to any tachycardia, the prematurityrequired to reset/entrain the tachycardia can be estimated. Therefore,in some circumstances (such as a very fast tachycardia), only one ATPattempt can be delivered prior to proceeding with cardiacdefibrillation. In these circumstances, the time differences betweenelectrodes can be combined with the conduction times when not intachycardia can be used to deliver a single ATP attempt with anincreased probability of minimizing tachycardia partial acceleration.

Additionally, when entraining a tachycardia, the pacing electrode(s) maybe far from the entrain site into areas of slow conduction. When theentrance site is far away from the pacing location(s), overdrive pacingmay advance much of the myocardium prior to advancing the entrance site.In these circumstances, the sensing electrodes and far-field pacingmorphology may not be helpful in identifying conduction slowing withincritical aspects of the reentrant circuit. Therefore, in yet anotherembodiment, the pacing electrode is selected using the time intervalsbetween electrodes during the tachycardia. In general, the latestoccurring electrode can be chosen. However, baseline conduction timesand far-field morphology can be measured and compared againsttachycardia time intervals and far-field morphology to determine theoptimal pacing electrode from which to pace. In yet another embodiment,ATP pulses can be delivered from both electrodes, and based on thefar-field morphology (or additional non-pacing electrode) the electrodeclosest to the entrance site can be used for subsequent pacingstimulations.

Therefore, the timing of tachycardia entrainment and the amount of delaywithin the reentrant circuit can be estimated by 1) measuringpost-pacing interval to failed ATP attempts 2) by analyzing the timingof intracardiac signals from a distal electrode within the chambers ofinterest, and/or 3) by far-field morphology analyses. Knowing this canbe used to optimize the first and subsequent ATP attempts.

Once the entrainment time and conduction delay is determined at acertain catheter location, the timing of tachycardia acceleration (andentrainment) can be determined at any overdrive pacing cycle length. Ourstudies have revealed that after adjusting for decremental conduction,the timing of entrainment can be estimated within a few milliseconds.Therefore, the entrainment time from the first or prior failed ATPattempt can be used to optimize subsequent ATP attempts. By knowingexactly when overdrive pacing will entrain the native tachycardia, thenumber of pacing stimulations can be limited in order to minimize thepossibility of tachycardia acceleration or fibrillation. Additionalpacing stimulations (after the tachycardia has been entrained and withstable conduction times) delay termination to the tachycardia, wastebattery life, and significantly increase the risk of developing fastertachycardias and/or disintegration into fibrillation.

Secondly (and of much more clinical importance), electrical restitutionproperties change with overdrive pacing. The first pacing stimulationthat reaches the arrhythmic circuit will accelerate the nativetachycardia by some fraction of time between the TCL and the PCL; whichis dependent upon many factors, including the distance between thepacing stimulation location and the reentrant tachycardia. If the firststimulation that reaches the arrhythmic circuit only partiallyaccelerates the tachycardia to the PCL, the electrical restitutioncurves dictate the critical aspects of the reentrant circuit are morelikely to tolerate the tachycardia when accelerated to the PCL. Therelationship between depolarization rates and repolarization times isknown as the electrical restitution curve. Therefore, partialacceleration may prepare the tachycardia to tolerate the ATP at fasteroverdrive pacing cycle lengths. The ATP algorithm can be set up suchthat the first pacing stimulation to accelerate the native tachycardiacompletely accelerates the tachycardia to the PCL (or desired interval).Delivering premature stimulations that only partially accelerate thenative circuit may accelerate repolarization rates and make thetachycardia more difficult to pace-terminate. Furthermore, by monitoringthe tachycardia in terms of tachycardia changes (such as tachycardiaacceleration) or tachycardia termination; an ATP attempt can deliverstimulations and measure the response. If the accelerating pulses do notterminate the tachycardia, the device can deliver one or morestimulation(s) at a longer cycle length (for example, based upon thetachycardia cycle length) followed by a paced cycle length at an evenshorter cycle length. Again, the tachycardia can be monitored forchanges or termination. Therefore, the device can continue pacing andadjusting the pulsing cycle length in order to facilitate tachycardiatermination without stopping the ATP attempt. By delivering pulses nearthe tachycardia cycle length, electrical restitution properties areleveraged to optimize tachycardia termination.

Current strategies of ATP can be improved by determining the exact timeof tachycardia acceleration from overdrive pacing. The first beat toreach the reentrant circuit will accelerate the native tachycardia.However, the amount of time the first beat accelerates the nativetachycardia will affect the ability of the ATP attempt to terminate thetachycardia. This is because the rate of cellular repolarization (therefractory period to the reentrant circuit) depends on the rate ofdepolarization. If the first stimulated wavefront to accelerate thetachycardia accelerates the native tachycardia by less than thedifference between the tachycardia cycle length (TCL) and the overdrivepacing cycle length (PCL); the partially accelerated tachycardia willprepare the tachycardia to tolerate the overdrive pacing cycle length(PCL). Therefore, by determining the amount of time required in order toaccelerate a tachycardia; the algorithm of overdrive pacing can beoptimized to increase the successfulness of the ATP attempt. Whileconduction velocities may slow at shorter pacing cycle lengths andtherefore serve to ‘protect’ critical aspects of the reentrant circuit;repolarization rates tend to be more sensitive than conductionvelocities in response to shortening diastolic intervals. That is tosay, premature stimulations rarely prolong conduction times across thecritical isthmus, even in tachycardias with very circuitous and delayedconduction times. Therefore, minimizing “partial acceleration” willfacilitate tachycardia termination, even with significant conductionvelocity slowing associated with the shorter pacing cycle length.

For example, measuring how much time pacing was required to entrain thetachycardia (e.g. as measured by distant electrodes or by far fieldmorphology changes), this time is the amount of time pacing must beadvanced from a given catheter in order to reach the arrhythmia. Byknowing the amount of time required to entrain the circuit, theanti-tachycardia pacing algorithm can be optimized. This can be used todetermine how many paced beats to initiate and the pacing interval(s) touse. The pacing intervals can be adjusted such that the entrance site isactivated at the same time the native arrhythmia meets the entrancesite. The following stimulated wavefront can be delivered to excite thearrhythmia circuit at a shorter pacing interval. However, as previouslymentioned, this tissue can be optimized by the prior pacing intervals toaccept the shortest possible pacing interval. This interval can bemathematically calculated and then optimized based on the time requiredto entrain the tachycardia. This pacing interval after the initialentraining stimulations can then be gradually shortened until thetachycardia is terminated. Various stimulation morphologies andalgorithms can also be used to optimize local capture.

Therefore, we have demonstrated that the timing of tachycardiaentrainment can be used to optimize the initial overdrive pacingalgorithm. Additionally, it is advantageous to improve the first ATPattempt. When entrainment has been obtained, the depolarized wavefrontsfrom the pacing electrode are able to reach the reentrant circuit. Adistal electrode and/or wavefront morphology analyses can oftendetermine when entrainment has been obtained and also if the tachycardiahas been terminated. This concept is discussed extensively in thesupplemental figures.

After obtaining entrainment, the pacing electrode can deliver a singleor multiple stimulations at the original tachycardia cycle length. Ifthis occurs, the pacing wavefront will reach the reentrant circuit atapproximately the same time as the native wavefront traveling in thereentrant circuit. Importantly, when pacing close to the tachycardiacycle length, the tachycardia cycle length determines the repolarizationrates within the tachycardia circuit. Therefore, an ATP attempt candeliver stimulations at a slower cycle length (such as the originaltachycardia cycle length) in order to delay the rate of repolarization.For example, an ATP attempt may deliver eight stimulations at PCL1.Far-field morphology and a distal electrode identify the tachycardia hasbeen entrained. The ATP algorithm can now deliver one or several pacingstimulations at the original tachycardia cycle length. This slower ratewill delay the rate of tissue repolarization; however, pacing maintainsaccess the pacing electrode has with the reentrant tachycardia. The ATPalgorithm can then deliver a single or several stimulations at a shortercycle length that rapidly and completely accelerates the tachycardia.Far-field morphology and the distal electrode can identify if thetachycardia has been terminated. If the tachycardia has not beenterminated, the device can deliver a single or several stimulations atthe tachycardia cycle length, followed by a single or severalstimulations at an even shorter cycle length than the previous attempt.This pattern can be repeated at shorter and shorter cycle lengths untilthe tachycardia is terminated. In this manner, only a single ATP attemptis required to terminate the tachycardia and also improves the abilityto terminate the tachycardia at any given paced cycle length.

Additionally, as previously discussed, the post-pacing, interval,far-field morphology analyses, and timing of signals from a distalelectrode in response to overdrive pacing can all be used alone or incombination with other methods to estimate the amount of conductiondelay within the tachycardia circuit. This conduction delay can be addedto the ‘priming’ stimulation, such that a single pacing stimulation atthe tachycardia cycle length plus the amount of tachycardia delay isdelivered after entrainment has been obtained. The priming stimulationslows the repolarization time within the tachycardia circuit whilemaintaining access for the pacing location to reach the reentrantcircuit. After the priming stimulation, an additional pacing stimulationwith a shorter pacing cycle length can then be delivered with a greaterprobability of tachycardia termination. Furthermore, tachycardiatermination, entrainment, and conduction delay within the reentrantcircuit can be estimated in order to deliver additional ‘priming’stimulations followed by a shorter stimulation. In this manner, the ATPalgorithm is reactive in the sense that responses from overdrive pacingare utilized in order to optimize the ATP attempt. This process can alsobe repeated to facilitate tachycardia termination. Sensing the timing ofentrainment or tachycardia termination can sometimes be difficult whenthe sensed time falls near the stimulation time. By having numerouselectrodes (such as a quadripolar left ventricular cardiacresynchronization lead), the various electrodes can increase theprobability the appropriate window for tachycardia assessment (bothentrainment and termination) will be present. By recording the successprior ATP attempts have had in terminating the defined tachycardia,repeating of a successful pacing algorithm can be performed; or, ifunsuccessful, the paced cycle lengths can be shortened.

A distal electrode and far-field morphology may or may not identifyentrainment and/or tachycardia termination. These abilities aredependent on a number of details specific to the tachycardia includingspatial relationships between electrodes and the native tachycardia andconduction properties within the myocardium. Fortunately, bi-ventricularpacing systems usually incorporate two electrodes, which are distantfrom each other. Having two electrodes distant to each other across themyocardium increases the probability that these electrodes will be ableto determine the timing of tachycardia entrainment, tachycardiatermination, and the amount of time delay within the reentranttachycardia.

One exemplary embodiment describes far-field morphologies, tachycardiarates, and timing differences between electrodes to identify variousreentrant tachycardias a patient may have. By accurately identifying thevarying reentrant tachycardias, prior ATP failures and attempts can usedto optimize subsequent ATP attempts.

In yet another embodiment, a second distal electrode within the heartcan be used to monitor the ATP attempt. Time changes in the tachycardiacycle length during pacing are used to adjust the next stimulated pacingcycle length. Once entrainment has been verified, the ATP algorithm candeliver one or more stimulations close to the baseline tachycardia cyclelength plus some percentage of the measured time delay within thecircuit (or a function related to one or both measurements), followed byone or more stimulations at a shorter pacing cycle length. The longpacing cycle lengths serve to ‘prime’ the reentrant tachycardia toprolong repolarization times in order to facilitate tachycardiatermination. With persistent pacing, the shorter cycle length may causeconduction delay within the reentrant tachycardia. The premature pacinggradually propagates through the areas of conduction decrement until allof the myocardium in the chambers of interest have the same interval.After delivery of the “priming” stimulation, the repolarization ratesprolong throughout the myocardium. Delivery of a pacing cycle length ata shorter cycle length is therefore at increased probability to reachmyocardial tissue that is refractory, particularly in areas critical tomaintain the reentrant tachycardia. Many tachycardias will experienceconduction slowing “time delay” within critical aspects of the reentranttachycardia prior to tachycardia termination. Therefore, by carefulmonitoring of far-field morphology or additional lectrodes not involvedin pacing, the processor can monitor for conduction slowing withincritical aspects of the tachycardia. The device can therefore monitorthe time delay occurring within the tachycardia. As long as the timedelay continues to prolong, the processor continues to deliver pacingpulses at largely the same pacing interval. However, if the time delayis stable within a specified interval, the device can proceed with nextsteps of the anti-tachycardia pacing algorithm (such as delivery of ashorter pacing cycle length or delivery of a ‘priming’ pacing pulse). Wedescribe methods where tachycardia entrainment, conduction delay, and/ortachycardia termination are estimated and used to optimize subsequentpacing cycle lengths.

FIG. 1 reveals a schematic diagram of a pacemaker/implantablecardio-defibrillator (ICD) with specialized leads going into the heartin which the present invention may be usefully practiced. In theembodiment shown in FIG. 1, there is a controller 40 designed to beimplanted into the body. The housing 42 of the device is connected toseveral leads that are designed to be implanted into the patient's heart90. The first lead 10 may include a proximal end 12 coupled to thehousing 42 and a second end sized for introduction into the patient'sheart 90, e.g., into the right atrium 92. The first lead may have adistal end 16 connected to a sensor and/or electrode 18 which can senseelectrical activity (depolarizations) and pace the right atrium 92, asprogrammed. In addition, the distal end of the first lead 10 may includeone or more features, e.g., a screw tip or other anchor (not shown) onthe distal end for securing the distal end relative to the right atrium92 or left atrium (not shown). One or more wires or other conductors mayextend from the distal end to the proximal end to communicate thesignals from the sensor 18 to the controller 40. Similarly, the secondlead 20 may include a proximal end 22 coupled to the housing 42 and asecond end sized for introduction into the patient's heart 90, e.g.,into the right atrium 92, through the tricuspid valve 95 and into theright ventricle 96. The second lead 20 contains a distal end 26 whichmay contain an electrode and/or sensor 28 designed to sense electricalactivity or deliver electrical energy to stimulate the right ventricle96. Similar to the first lead 10, the second lead 20 may include one ormore features, e.g., a screw tip or other anchor, on the distal tip tosecure the distal end within the patient's heart 90, e.g., the wall ofthe heart 90 within the right ventricle 96, similar to pacing leads.Alternatively, the first and second leads may be provided on a singledevice with a branch distal end (not shown), similar to otherembodiments herein. Additionally, there may be a third lead 30 with aproximal end 32 in order to couple the lead to the housing 42. The thirdlead may contain a second end sized for introduction into the patient'sheart 90, e.g., into the right atrium 92, through the coronary sinus 97or other vein of the heart 90. This lead may contain a sensor orelectrode 34 designed to sense or deliver electrical activity. Thissensor or electrode 34 may sense and/or deliver electrical activity toeither the atrial or ventricular tissue. In addition, the third lead 30may contain a distal end 36 coupled to an additional sensor or electrode38 to sense and deliver electrical activity to a different location inthe heart 90. Similar to the first lead 10 and second lead 20, the thirdlead 30 may include one or more features, e.g., a screw tip or otheranchor, on the distal tip to secure the distal end within the patient'sheart 90, e.g., within a distal vein of the coronary sinus 97, similarto typically used pacing leads. This lead may sense and pace electricalactivity occurring in the left ventricle 98. In addition, if there is atachycardia occurring within the right ventricle 96 or the leftventricle 98, the sensors or electrode 28, 34, or 38 may sense and/ordeliver electrical activity in order to terminate the tachycardia. Inaddition, if there is a tachycardia occurring within the right atrium 94or left atrium (not shown), the sensors or electrodes 18 or 34 may senseand/or deliver electrical activity to terminate the tachycardia. Theelectrodes 18, 28, 34, or 38 are used to illustrate the delivery ofanti-tachycardia pacing (ATP) therapy throughout this description,although any number of electrodes are capable of sensing and deliveringelectrical energy to the heart 90. The ATP therapy may be used to treatventricular as well as atrial tachyarrhythmias.

FIG. 2 shows a simplified functional block diagram of one embodiment ofthe components located within and connected to the controller 40. Thecomponents include a control processor 52 which receives inputinformation from various components in order to determine the pacingalgorithm in order to treat the patient. The control processor isconnected to pacing circuitry 53, defibrillation circuitry 55, memory52, and a telemetry interface 55. The pacing circuitry 53 and thedefibrillation circuitry 55 connects to the first lead 10, second lead20, and third lead 30; and ultimately connects to the electrodes, (forexample, 18, 28, 34, and 38). These connections allow for multiplecapacities to sense electrical activity (such as myocardialdepolarizations), deliver pacing stimulations, and/or deliverdefibrillation or cardioversion shocks. Based on the input received fromthe electrodes 18, 28, 34, and 38 through the pacing circuitry 53, thecontrol processor 51 performs calculations to determine the propercourse of action, which may include providing ATP therapy to one or moreelectrodes, providing defibrillation or cardioversion shocks to one ormore electrodes through the defibrillation circuitry 55, or no therapyat all. The control processor 51 is connected to a telemetry interface96. The telemetry interface can wirelessly send and receive data from anexternal programmer 62 which is coupled to a display module 64 in orderto facilitate communication between the control processor 51 and otheraspects of the system external to the patient. The control processor 51may continue to sense electrical activity from one or more electrodeswhile deliver pacing stimulations to other electrodes. The controlprocessor 51 may store selected data to memory 52, and retrieve storeddata as necessary. For example, the control processor 51 may identifykey aspects of a tachyarrhythmia in order to effectively differentiatethe tachycardia and other key aspects of the tachyarrhythmia in order tooptimize the best therapy in order to terminate the tachyarrhythmia.

FIG. 3 is a graphical representation of overdrive pacing from oneelectrode while sensing electrical depolarizations from a secondelectrode. The Fig helps demonstrate how timing measurements can beperformed to estimate the Time to Entrainment. The time to entrainmentis the total amount of time overdrive pacing must ‘gain’ on the nativetachycardia in order to reach and then accelerate the tachycardia.Therefore, as demonstrated in FIG. 3, the time to entrainment can beestimated by measuring the timing of sensed electrical activity on asecond, distal electrode. For example, if a tachyarrhythmia occursbetween two electrodes inside of a heart, one electrode may deliver ATP.As soon as the delivered electrical activity creates a depolarizingwavefront that reaches and accelerates the native tachycardia, thesecond electrode can determine this event. In this event, for example,the time to entrainment can be estimated by adding the prematurity ofeach paced stimulation (TCL−PCL) minus the amount of tachycardiaacceleration. Therefore, the time to entrainment can be estimated as the(TCL−PCL) times the number of pacing stimulations required to entrainthe tachycardia minus the amount of tachycardia acceleration on thefirst entrained stimulation. There may be delay in the tachycardia dueto the shorter paced cycle length. This delay can be estimated byslowing the overdrive pacing cycle length, for example the paced cyclelength can be prolonged to approximate the tachycardia cycle length.Another method to estimate the time to entrainment is by summing thedifference in time between the paced stimulations and the senseddepolarizations. Again, conduction delay needs to be taken into account.

Another method involves measuring the difference in time before pacingand during entrainment (or the first entrainment) between the pacingelectrode to the sensing electrode. This time difference is similar tothe time described by the N+1 difference (Soejima et al, 2001).

In yet another embodiment, the time to entrainment can be estimated bythe return cycle of a failed ATP attempt minus the tachycardia cyclelength. The return cycle can also be measured by a specific pacingmaneuver designed to determine the time to entrainment while minimizingconduction delay within the circuit. For example, the ATP pacingalgorithm may deliver a number stimulations until entrainment wouldlikely to have occurred or with evidence of entrainment; followed bydeliver of pacing stimulations at a cycle length approximating thetachycardia cycle length. When pacing close to the tachycardia cyclelength, the time delay between the stimulation to the sensed electricaldepolarization (or far-field morphology analyses demonstrated in FIG. 4)can be used to estimate the time to entrainment. Alternatively, ATP canbe stopped; and the resulting post-pacing interval (PPI) or the returninterval can be measured to estimate the entrainment time by calculatingthe PPI minus the tachycardia cycle length. As previously mentioned, theTime to Entrainment can also be estimated by two entrainment maneuversby electrodes on opposite sides of the reentrant circuit. Of note, asdemonstrated in FIG. 3, the third stimulation brings in the senseddepolarization sensed by the sensing electrode. The next interval seenon the sensing electrode has an interval equal to the PCL. Thisdemonstrates that any delay that may have occurred in the pacedstimulation on the first entrained stimulation was similar on the secondentrained stimulation. However, if the interval measured on the sensingelectrode were longer than the PCL, this delay would suggest conductiondelay along the path between the pacing electrode and sensing electrode.This embodiment is discussed in more detail in FIG. 10; where this timedelay may be utilized to adjust the pacing algorithm in order tofacilitate tachycardia termination.

FIG. 4A and FIG. 4B reveal an example of intracardiac and far-fieldmorphologies which illustrate how far-field morphology analyses can beutilized to estimate the Time to Entrainment. FIG. 4A reveals thefar-field morphology occurring in three different scenarios. The firstcolumn demonstrates the far-field morphology occurring when pacing atbaseline (when no underlying tachycardia is present). The second columnreveals far-field morphology occurring during a tachycardia. In thisfigure, the timing of the sensed depolarization occurring on theelectrogram can be determined in relation to the far-field morphology.In the third column, the entrained far-field morphology is shown. InFIG. 4B, the far-field morphologies are superimposed such that thewaveforms overlap. Various computational algorithms and programs can beperformed to determine the various off-set required to minimize thedifference between waveforms. In yet another embodiment, the waveformanalyses can determine the offset required such that the sum of thebaseline paced morphology and the baseline tachycardia are arranged suchthat the sum of these waveforms approximate the entrained tachycardia.When this occurs, the time offset between the paced stimulation and thesensed depolarization on the pacing electrode can be used to estimatethe Time to Entrainment. As previously mentioned, this time can be usedto optimize the pacing algorithm. Furthermore, with continued pacing,the off-set may prolong indicative of conduction delay occurring withinthe path of electrical conduction.

FIG. 5 a simplified diagram of a reentrant tachycardia circuit within aheart and several pacing electrodes for sensing and/or deliveringelectrical stimulations according to an embodiment of the presentinvention. This figure demonstrates a key concept in utilizing more thanone electrode to optimize ATP algorithms. In this figure, the plane ofthe figure represents myocardial tissue capable of propagatingdepolarizing wavefronts. In this embodiment, there are three electrodes,E1, E2, and E3, each capable of sensing and delivering electricalactivity. There is a scar between the electrodes that does not conductelectrical activity. Additionally, there is a an area of slowconduction, within the scar, that is able to conduct electricalactivity, but slower than the other, healthier, myocardial tissue. Inthis example, a reentrant tachycardia can be created which is capableperpetual circular movement through the area of slow conduction and thenaround the scar. When an electrode obtains tachycardia entrainment, forexample, electrode E1, the Time to Entrainment, is roughly the time ittakes for the paced stimulation to leave the pacing location (Time E1_(O)) to the “entrance site,” plus the time it takes for electricalactivity to leave the native circuit from the “exit site” to the pacinglocation (Time E1 _(R)), minus the time it takes to travel in thetachycardia circuit between the exit site and the entrance site (Time E1_(Y)). Therefore, the Entrainment Time for electrode E1 is roughly E1_(O)+E1 _(R)−E1 _(Y). During pacing at an unchanging pacing cyclelength, there will be fusion between the wavefront created from thepacing location and the wavefront created when leaving the tachycardiaexit site. These wavefronts collide at various locations depending oncircuit morphology, conduction velocities, and other variables. Prior tothe tachycardia, the time it takes to conduct electrical signals fromone electrode to the others can be measured. For example, pacing fromelectrode E1 will be sensed by electrodes E2 and E3; and the time delaybetween stimulation and sensing the depolarizations from these otherelectrodes can be measured. Given conduction velocities can be variabledepending on the pacing cycle length; these time delay can be recordedat various cycle lengths and therefore not necessarily constant. Whenentrainment has been obtained, the location of wavefront collision (akafusion) is dependent on a number of variables including the tachycardiacycle length and the pacing cycle length. If entrainment is obtained butthe wavefront from the stimulating electrode reaches the distalelectrode, this electrode will not be able to determine the timing ofentrainment or the Time Delay that may occur in the circuit. The systemtherefore can measure the baseline conduction time that is required totravel from the pacing electrode (E1) to any other electrode (EX):StimTime_(E1->EX). In addition, during the tachycardia, the time delaybetween the sensed signals occurring between the electrode that willpace (E1) and any other electrode (EX) can be measured during thetachyarrhythmia: ReentrantTime_(E1->EX). The ability of a distalelectrode EX to determine the timing of entrainment (as well as TimeDelay in the circuit), can be estimated by equation 7 below. TheReentrant Time is the difference in time to leave the exit site andtravel to both the pacing electrode E1 and any other electrode EX.

Cannot verify entrainment if:

Time to entrainment−(TCL−PCL)−Time Delay

>Stim Time_(E1→EX)−Reentrant Time_(E1→EX)   (7)

Therefore, by having more than two electrodes, the probability of havingan electrode capable of sensing entrainment is increased. Furthermore,even when the electrode satisfies equation 7; the timing of sensinglocal signals can be missed [blanked] if the sensing occurssimultaneously with the timing of pacing. Therefore, additionalelectrodes, even close in proximity, can augment the probability thetiming of entrainment can be determined, as well as estimation of TimeDelay within the circuit. Furthermore, if the pacing entrance site isclose in proximity to the tachycardia exit site, far-field morphologyanalyses may be limited in its ability to estimate the Time toEntrainment and potential Time Delay. With one or more distal electrodescapable of measuring the entrained tachycardia, the system can estimateentrainment, time delays in the circuit, and tachycardia termination. Bycorrectly measuring and/or estimating these components, ATP pacingalgorithms do not need to stop pacing until the tachyarrhythmia isterminated. This describes another example in which ATP algorithms canbe optimized to more rapidly and efficiently terminate tachyarrhythmias.

In yet another embodiment, the system may be able to design the initialanti-tachycardia pacing algorithm based on some measurements. Forexample, by recording the baseline conduction time from the pacingelectrode to at least one additional electrode, and measuring thedifference in time between these two electrodes during an episode oftachycardia, the Time to Entrainment may be estimated as the differenceof these measurements. This method requires certain assumptionsregarding the reentrant circuit and its relationship to the pacingelectrodes; however, this method creates a rapid initial ATP algorithmthat has a high probability of tachycardia termination. In yet anotherembodiment, having the device routinely measure conduction times betweenelectrodes, the device may monitor and assess for ischemic episodes.This is because ischemia can change conduction times. Therefore, duringa myocardial infarction, the conduction times may change. Therefore,monitoring conduction times may serve as an indicator of ischemia andcan alert the patient or care-takers to take action.

FIG. 6 reveals the relationship between the coupling intervals during apacing drivetrain and the effective refractory period, also known as theelectrical restitution curve. FIG. 6 demonstrates a typical electricalrestitution curve seen in ventricular myocardial tissue. In this figure,a pacing train was performed at two cycle lengths, 400 ms and 600 ms.Then, a coupling stimulation was delivered at various intervals (x-axis)which was followed by a second stimulation S2. The coupling intervalpredicts the interval of the second stimulus that fails to capture themyocardium (the effective refractory period or ERP). Note howsignificantly a single coupling interval dramatically affects the ERP ofthe second premature stimulus. For example, when deliver a pacing trainat 400 ms, a single stimulus at 230 ms is refractory (does not conduct)in the majority of patients. However, if a pacing train is delivered at400 ms, followed by a coupling interval of 260 ms, the stimulus at 230ms no longer is refractory for any of the patients in this study. Inorder to terminate the majority of patients, the second stimulus needsto shorten by over 40 ms, and stimulate at less than 190 ms in order toreach refractoriness. The electrical restitution curve reveals howdramatically repolarization rates are determined by the previousdepolarization interval.

FIG. 7 is a graphical representation demonstrating the relationshipbetween the pacing prematurity (TCL−PCL), the number of pacingstimulations, the Time to Entrainment, and the amount of tachycardiaacceleration on the first entrained stimulation. This figuredemonstrates the importance the electrical restitution curve indesigning ATP algorithms. In order to ‘gain’ on the native tachycardia,ATP must pace faster than the TCL. Each paced stimulation gains on thetachycardia by the difference between the TCL and the PCL (the “pacingprematurity). ATP or overdrive pacing begins to accelerate thetachycardia when the sum of the pacing prematurity is greater than theTime to Entrainment. The first stimulation that accelerates thetachycardia, however, can shorten the TCL by any amount between the TCLand the PCL. With perpetual pacing, the entire tachyarrhythmia willaccelerate to the PCL; however, the first stimulation that entrains thetachycardia may only partially accelerate to the PCL. Since the goal ofATP is to reach electrical refractoriness within the reentrant circuit;this partial acceleration can prepare the tissue involved in thereentrant circuit to repolarize more quickly. Based on mathematicallymodeling and empirical testing, the amount of acceleration on the firstentrained stimulation will dramatically effect whether or not thetachyarrhythmia is terminated at any given PCL. With knowledge of theTime to Entrainment, the prematurity can be arranged such that the firststimulation that accelerates the tachycardia will accelerate thetachycardia to the desired PCL. This arrangement can minimize thepartial acceleration occurring on the first entrained stimulation; andhelp optimize the probability of tachycardia termination.

FIG. 8 reveals an example of utilizing intracardiac measurements andfar-field morphology analyses to determine the Time to Entrainment andTime Delay within the circuit taken from an ATP attempt from anepicardial electrode. In this example, two electrodes are located onroughly opposite sides of a reentrant tachycardia. Pacing is initiated,and the third stimulation reveals the signal was brought in on thedistal electrode channel. As discussed previously in relation to FIG. 3,various measurements can be performed at this point to estimate the Timeto Entrainment. Furthermore, far-field morphology analysis revealed (aspreviously discussed in FIG. 4) the overlapping time gain to accelerateby less than predicted by the difference between the TCL and PCL; andtherefore the entrainment time can be estimated. Furthermore, as can beseen in the figure, the fourth stimulation also entrained the reentranttachycardia, however, the stim to sense timing prolonged from 281 ms to290 ms. On far-field morphology, the stim to far-field minimum alsoprolonged by 9 ms. Therefore there was 9 ms delay somewhere between thepacing electrode and the sensing electrode, usually in areas of slowconduction. These areas of slow conduction usually occur at criticalaspects of the reentry tachycardia. In one embodiment (which may beprogrammable), the device can sense this delay in conduction andcontinue pacing as long as conduction delay continues to prolong fromoverdrive pacing (as evidenced from far-field morphology analyses or atleast one additional electrode). The device can therefore estimate andrecord the Time Delay that is occurring.

FIG. 9 reveals a flow chart of one embodiment to determine the ATPtherapy. In Step 1, the device assesses and records the baselineconduction times to various electrodes and pacing morphologies from oneor more of the electrodes when the patient is not in tachycardia. Thesemeasurements are used for reference when determining if ATP therapiesare able to determine entrainment from additional electrodes orfar-field pacing morphology analyses.

In Step 2, the device is programmed to monitor for tachycardia. In Step3, the device determines the patient is now in a tachyarrhythmia. Thecriteria of determining criteria for tachycardia have been previouslydescribed. In addition, using the timing differences between more thanone electrode; and the timing differences between far-field morphologyanalyses and local activation can help identify and mathematicallydescribe tachyarrhythmias. Additionally, these specific measurements canbe recorded and used to identify and differentiate tachyarrhythmias.Later in the algorithm, the device can record the Time to Entrainmentfrom one or additional electrodes and record the Time to Entrainment fora specific electrode for a specific tachyarrhythmia.

In Step 4, the device assesses whether the newly identifiedtachyarrhythmia has been previously identified. As mentioned, this isdetermined by comparing time differences and morphology analyses. If thetachycardia has not been previously identified, we move to Step 5, wherethe initial ATP algorithm is determined based on the tachycardia cyclelength and timing differences between electrodes. For example, theability to determine entrainment is related to the difference in timebetween the sensed local activation and the paced time delays betweenelectrodes. The device could determine which electrodes have thegreatest probability of being located on opposite sides of the reentrantcircuit. In addition, the device may be programmed to deliver ATP fromthe latest (or earliest) local activation or in relation to baselinetiming differences.

If the original tachycardia had been previously identified, we move fromStep 4 to Step 6. In this Step, previously successful and unsuccessfulATP attempts can be incorporated into the device to determine the firstATP pacing algorithm. In addition, as previously discussed, recordedTime to Entrainments for this particular tachycardia can be used suchthat the pacing prematurity is arranged such that the first pacingstimulation to accelerate the native reentrant circuit fully acceleratesthe reentrant circuit by the difference between the TCL and the chosenPCL. In this manner, partial acceleration is minimized. The firststimulation that accelerates the tachycardia can be shortened if priorattempts failed to terminate on the first accelerating stimulation. Inaddition, if the first stimulation attempting to accelerate/terminatethe tachyarrhythmia fails to capture, the pacing prematurity can bearranged to facilitate local capture. This can be done by graduallyincreasing the pacing prematurity as a way of ‘priming’ local myocardiumto accept the shorter paced cycle length.

Regardless of the ATP pacing algorithm, both Step 5 and Step 6 move toStep 7 and deliver the ATP as programmed. Timing delays from distalelectrodes, far-field analyses, and evoked potentials can be used todetermine local capture. Additionally, the return cycle can be used todetermine if the pacing stimulations captured the myocardium.Additionally, the exact stimulation which did not capture the myocardiumcan be identified and used to adjust the ATP pacing strategy.

FIG. 10 further reveals a flow chart of one embodiment that may occuronce the device delivers ATP in Step 7. At Step 8, the device maymonitor and/or perform far-field morphology analyses and the timemeasurement from the timing of stimulation to local capture measuredfrom electrodes. Until entrainment occurs, these measured times shouldprolong by the pacing prematurity unless the stimulated wavefront timedirectly reaches the electrodes. This time measurement, as previouslydescribed, is recorded prior to the patient going into thetachyarrhythmia. Therefore, the device can determine if the measuredpremature signal occurs from direct signal propagation versus theentrained wavefront from the native tachycardia. In Step 9, during anATP attempt, the device is constantly assessing for evidence oftachycardia termination, a significant change in the tachyarrhythmia, ortachycardia acceleration. If either of these circumstances are met, thedevice may stop pacing and re-assess the rhythm as in Step 10.Tachyarrhythmia termination, change, or acceleration may be monitored byfar-field morphology analyses and/or the rate and relationship amongsensed signals from various electrodes.

In Step 11, once the ATP is stopped, the device will measure the returncycle length, determine if the patient remains in a tachyarrhythmia,categorize the most recent pacing strategy was successful orunsuccessful at terminating the tachyarrhythmia. If unsuccessful, thedevice may shorten the pacing cycle length (PCL) to be more aggressiveor change the pacing location depending on the settings programmed intothe device.

Now moving back to Step 8, the device may obtain evidence that the ATPattempt has successfully entrained the tachyarrhythmia as in Step 12. Atthis point, the device will estimate the Time to Entrainment for thisidentified tachyarrhythmia and use this measurement should thistachyarrhythmia be identified again and attempt to deliver therapy. Inone embodiment, the device proceeds to Step 13, where the devicecontinues to deliver pacing stimulations as long as the device measuresa prolonging Time Delay. The Time Delay is estimated by a prolongationof stimulation to sensed signal (either from a second electrode or fromfar-field morphology analyses). The amount of prolongation the deviceidentifies as significant can be preprogrammed and adjustable. Often,however, persistent pacing at a constant cycle length will graduallyslow in critical aspects of the arrhythmic circuit and then finallyterminate the tachycardia. The first stimulation that does not conductthrough the arrhythmic circuit in the orthograde direction can bedetected by the device in terms of far-field morphology or a distalelectrode as long as the conduction times satisfy equation 7 at whichpoint the device may transition to Step 9.

Once the Time Delay is minimal or less than the programmed determinedamount of time, in one embodiment, the device may deliver one or morestimulations at the TCL plus the amount of measured Time Delay as inStep 14. In another embodiment, the device may deliver this primingstimulation at an interval that is determined by the TCL and/or the TimeDelay but not necessarily the TCL or the sum of the TCL plus the TimeDelay. This priming stimulation prolongs the interval seen by criticalaspects of the reentrant circuit while maintaining access to thearrhythmic circuit by the pacing electrode. After delivering one or morepriming stimulations, the device can then deliver a pacing stimulationat a shorter pacing cycle length with an increased probability oftachycardia termination. This interval may be the same pacing cyclelength (PCL) as the prior pacing stimulation(s) or may be adjusted basedon programmable or algorithmic features.

If the tachyarrhythmia does not terminate on this stimulation the devicemay transition back to Step 13 and continue pacing at the PCL; or thedevice may proceed to Step 15, where the device may shorten the PCLafter the priming stimulation. Alternatively, the device may deliveradditional priming stimulations, change the pacing location, or stoppacing altogether. The decision tree can be adjustable based on the TCLand prior attempts. That is, with shorter TCL, the device may be moreaggressive by shortening the PCL rapidly. Alternatively, if thetachyarrhythmia is prone to tachycardia acceleration or fibrillation,the device may shorten the PCL more gradually. Each of the steps S13,S14, and S15 are all working in tandem such that the device isdelivering ATP while adjusting the ATP based on measured responses fromother electrodes or far-field morphology analyses. Furthermore, thedevice may sense changes in the signals consisted with tachycardiatermination (moving to Step 9) or lose the ability to identifytermination, in which case the system moves to Step 10.

In Step 10, the timing relationships between electrodes do not satisfyequation 7; or the far-field morphology analyses reveals the pacingmorphology (gradual fusion) to match the morphology with isolated pacingin the absence of an underlying tachycardia. This can occur when thetachycardia morphology is similar to the paced morphology from thepacing electrode or when the entrance and exit locations for theentrained tachycardia are close in proximity. In this situation, thedevice cannot definitively determine when the tachycardia has terminatedor accelerated. Therefore, the device must occasionally stop delivery ofATP in order to assess the heart and the rhythm. In these circumstances,the device may move to Step 16, where ATP is driven by protocol. Inaddition, the device can deliver enough pacing stimulations sufficientto obtain entrainment.

In one embodiment, the device may deliver one or more stimulations closeto the TCL (“priming stimulations”) followed by one or more stimulationsat a shorter cycle length. Alternatively, the device may simply stop ATPand (moving to Step 17), measure the return cycle (the post-pacinginterval). This interval can be used to 1) verify the tachycardia wasentrained and 2) determine the Time to Entrainment. When the tachycardiarequires more than two attempts to pace terminate the tachyarrhythmia,the resulting return cycle length can be measured as well as any TimeDelay associated with the shorter cycle lengths. In one embodiment, apriming stimulation utilizing the Time Delay can be delivered tofacilitate tachycardia termination even when entrainment cannot beverified during pacing. Again, the Time to Entrainment can be used toarrange the initial pacing stimulations to minimize partial accelerationon the first accelerating pacing stimulation.

After delivering ATP and measuring the return interval, the device canreturn to Step 2 and assess the tachyarrhythmia. The device can identifyif the prior ATP strategy was successful or unsuccessful and use thisinformation to guide the ATP algorithm.

FIG. 11 is a graphical representation of deliver an anti-tachycardiapacing therapy according to one embodiment of the present invention.Depolarizations or signals sensed by the pacing channel electrode arelabeled S1 and S2. The distal channel electrode has a line when itsenses depolarizations or signals. ATP pulses are labeled with ATP1being the first pacing stimulation and ATPS is the last pacingstimulation. The time interval between the first and second sensedsignals is the tachycardia cycle length (TCL). The TCL, the timingdifferences between electrodes, and the far-field morphology (not shown)can be used to identify the tachycardia (“Tachycardia Identifiers”). Thesensed signals can alert the Control Processor of the tachycardia anddetermines the ATP pacing strategy. The device begins delivering ATPpulses. If the Time to Entrainment had previously been recorded for thistachycardia, the device would arrange the initial pacing prematuritysuch that the sum prematurity is equal to the Time to Entrainment. Thefollowing pacing stimulation would then completely accelerate thearrhythmic circuit by the pacing prematurity of that paced stimulation(TCL−PCL).

In FIG. 11, the third pacing stimulation brings in the sensed signal onthe distal channel. Assuming this time is shorter than the previouslyrecorded conduction time between these electrodes, this would suggestthe tachycardia has been entrained, which may signal to the processorthe tachycardia is now being advanced by the pacing stimulations. Thepacing prematurities can be summed to the point of tachycardiaadvancement to estimate the Time to Entrainment; alternatively thedifference in time from the Stim to sensed signal on the distal channelbetween the first entrained stimulation and the baseline tachycardia canbe used to estimate the Time to Entrainment. In the graphicalrepresentation, note the fourth pacing stimulation should be completelyentrained (advanced to the pacing cycle length), however, there is aprolongation in the stimulation to sensed time on the distal channel.This prolongation can be attributed to conduction delay within themyocardium and can be used to estimate the Time Delay (TD1). The fifthATP pacing stimulation notes a stable Time Delay. Therefore, in oneembodiment, the device delivers a “Priming” stimulation, by delivering astimulation with the interval of the TCL plus the TD1 (or somepercentage of the TCL plus the TD1). In yet another embodiment, thedevice may deliver one or more pacing stimulations at the originaltachycardia cycle length or substantially similar to the tachycardiacycle length.

In other embodiments, this “priming” stimulation can deliver one or morepacing stimulations at or near the TCL. The device then delivers apacing stimulation with a shorter interval. In this example, thetachycardia does not terminate (there is a sensed signal from ATP 7) andthere was no measured conduction delay (the interval equals the PCL).Had the device measured a conduction delay, the device could havecontinued delivering ATP therapy at the same PCL. In the currentembodiment, the device delivers a second “priming” stimulation, followedby a PCL at a shorter cycle length (PCL2). In this example, the sensedsignal on the distal channel does not sense a signal (the amount ofdelay deemed significant can be programmed) and therefore can identifythe tachycardia as terminated and pacing is stopped in order to assessthe rhythm.

Sometimes, the Time Delay measured occurs from conduction changes orcircuit changes at locations other than the arrhythmic circuit, forexample, near the pacing electrode. In this scenario, delivering primingstimulations at the TCL plus the TD1 will result in loss of entrainmentto the arrhythmic circuit. The time interval between the stimulation andthe sensed signal on the distal channel can be used to identify and theATP pacing algorithm can be adjusted to correct for this. In FIG. 11,note the sensed signals sometimes occur simultaneously with the ATPstimulations. When this occurs, crosstalk can prevent this signal frombeing measured. Therefore, as previously discussed, sensing from morethan one sensing channels can help monitor the tachyarrhythmia duringATP therapy. Therefore, the multiple sensing electrodes can be used incombination (and in conjunction with far-field morphology analyses) toassess for entrainment, conduction delay, and changes in thetachyarrhythmia (such as termination or acceleration). Therefore, in oneembodiment, catheters with two or more electrodes are described in orderto sense cardiac depolarizations from more than one location in order toavoid sensing issues (blanking), which may occur when otherwise sensingfrom one location.

While the invention is susceptible to various modifications, andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that the invention is not to be limited to the particular formsor methods disclosed, but to the contrary, the invention is to cover allmodifications, equivalents and alternatives falling within the scope ofthe appended claims.

1. A method for delivering therapy using an implant including aprocessor and one or more electrodes implanted in a patient's bodyadjacent a heart to terminate a tachycardia event, comprising: sensingcardiac signals from the heart and detecting at the processor areentrant tachycardia event in response to the sensed cardiac signals;delivering one or more pacing pulses to the heart via one or more pacingelectrodes having one or more pacing cycle lengths sufficient to advanceor terminate the tachycardia; monitoring paced morphology of the heartduring the delivery of the one or more pacing pulses to identifytachycardia termination/block; and adjusting the delivery of pacingpulse(s) in response to the monitored paced morphology.
 2. The method ofclaim 1, further comprising recording far-field paced morphology of theheart when not in a reentrant tachycardia in order to assist inmonitoring the reentrant tachycardia.
 3. The method of claim 2, furthercomprising, if the processor estimates the tachycardia has beenentrained by the one or more pacing pulses, continuing to deliver pacingpulses at cycle lengths substantially similar to the one or more pacingcycle lengths and measuring interval changes using far-field morphologyanalyses.
 4. The method of claim 3, wherein continuing to deliver pacingpulses comprises: delivering one or more priming pulses with one or morepriming pulse intervals longer than the one or more pacing cycle lengthsused to advance/entrain the tachycardia via the one or more pacingelectrodes; and thereafter, delivering at least one accelerating pulsewith one or more accelerating pulse intervals shorter than the one ormore priming pacing pulse intervals to the heart via the one or moreelectrodes.
 5. The method of claim 4, further comprising: if theprocessor does not identify the tachycardia has terminated or unable toidentify that the tachycardia has terminated, continuing to alternatebetween delivering one or more priming pulses followed by at least oneaccelerating pulse; and wherein at least one accelerating pulse intervalis shortened with each iteration.
 6. (canceled)
 7. A system fordelivering therapy to terminate a tachycardia event in a heart of apatient, comprising: a pacing device configured to be implanted in thepatient's body and comprising a processor; a plurality of electrodescoupled to the processor and sized for implantation within the patient'sbody; wherein the processor is configured to: sense cardiac signals fromthe heart and detect a tachycardia event in response to the sensedcardiac signals; deliver one or more pacing pulses to the heart via oneor more pacing electrodes having one or more pacing cycle lengthssufficient to advance or terminate the tachycardia; monitor cardiacsignals during the delivery of the one or more pacing pulses to identifyat least one of the following: pacing pulse did not advance thetachycardia, tachycardia advancement/entrainment in response to pacingpulse, tachycardia termination/block within the reentrant circuit,tachycardia acceleration faster than the one or more pacing cyclelengths, or inconclusive evidence for tachycardia advancement ortermination; and adjust the delivery of pacing pulse(s) in response tothe monitored cardiac signals.
 8. The system of claim 7, wherein theprocessor is further configured to record one or more conductionintervals from the one or more pacing electrodes to the one or moremonitoring electrodes when not in a reentrant tachycardia and/or thefar-field paced morphology when not in a reentrant tachycardia in orderto assist in monitoring the reentrant tachycardia.
 9. The system ofclaim 8, wherein the processor is further configured to estimate whenthe tachycardia has been advanced/entrained by paced pulses, continue todeliver pacing pulses at cycle lengths substantially similar to the oneor more pacing cycle lengths, and measure the time delay correspondingto conduction delay within and outside of the reentrant circuit bymeasuring interval changes between the one or more pacing electrodes andthe at least one sensing electrode or by using far-field morphologyanalyses.
 10. The system of claim 9, wherein the processor is furtherconfigured to adjust the delivery of pacing pulses to include deliveringone or more priming pulses with one or more priming pulse intervalslonger than the one or more pacing cycle length used to advance/entrainthe tachycardia via the one or more pacing electrodes, and, thereafter,delivering at least one accelerating pulse with one or more acceleratingpulse intervals shorter than the one or more priming pacing pulseintervals to the heart via the one or more electrodes.
 11. The system ofclaim 10, wherein the processor is further configured such that, ifprocessor does not identify the tachycardia as terminated nor loses theability to identify tachycardia termination, the processor continues toalternate between delivery of at least one priming pulse with a longerpulse interval followed by at least one accelerating pulse at a shorterpulse interval; and wherein at least one accelerating pulse interval isshortened with each iteration such that the measured amount of timedelay is unchanged for consecutive accelerating pacing pulses within aspecified threshold. 12-13. (canceled)
 14. A system for deliveringtherapy to terminate a tachycardia event in a heart of a patient,comprising: a pacing device configured to be implanted in a patient'sbody and comprising a processor; a plurality of electrodes coupled tothe processor and sized for implantation within the patient's body;wherein the processor is configured to: sense cardiac signals from theheart via one or more electrodes of the plurality of electrodes anddetect a ventricular tachycardia in response to the sensed cardiacsignals having a tachycardia cycle length; deliver a plurality ofoverdrive pacing pulses to the heart via one or more pacing electrodes,the overdrive pacing pulses having overdrive pacing cycle lengthssufficient to advance or terminate the tachycardia; monitor cardiacsignals via one or more sensing electrodes spaced apart from the pacingelectrodes while delivering the overdrive pacing pulses to identifylocal depolarization of the heart after each overdrive pacing pulse bythe one or more sensing electrodes; measure time intervals betweensensed local depolarizations identified by the one or more sensingelectrodes; and adjust delivery of the overdrive pacing pulses based atleast in part on the time intervals between the sensed localdepolarizations.